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As recent studies have brought attention to macrofollicular patterns, atrophic changes, and papillary structures as being associated with\n                    <jats:italic>DICER1<\/jats:italic>\n                    mutations, we sought to explore these observations in a bi-institutional cohort. A total of 61 thyroid lesions (54 tumors and 7 cases of thyroid follicular nodular disease; TFND), including 26\n                    <jats:italic>DICER1<\/jats:italic>\n                    mutated and 35\n                    <jats:italic>DICER1<\/jats:italic>\n                    wildtype controls were subjected to histological re-investigation and clinical follow-up.\n                    <jats:italic>DICER1-<\/jats:italic>\n                    mutated lesions showed a statistically significant association with younger age at surgery (29.2\u2009\u00b1\u200912.5 versus 51.3\u2009\u00b1\u200918.8,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0001), a predominant macrofollicular growth pattern (20\/26 mutated cases versus 18\/35 wildtype;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01) and atrophic changes (20\/26 mutated cases versus 2\/35 wildtype;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0001). Similar results were obtained when excluding TFND cases. We also present clinical and histological triaging criteria for\n                    <jats:italic>DICER1<\/jats:italic>\n                    sequencing of thyroid lesions, which led to the identification of\n                    <jats:italic>DICER1<\/jats:italic>\n                    variants in 16 out of 26 cases (62%) when followed. Among these, 3 out of 12 cases with available data were found to carry a constitutional\n                    <jats:italic>DICER1<\/jats:italic>\n                    mutation. This observation suggests that the majority of\n                    <jats:italic>DICER1<\/jats:italic>\n                    mutations are somatic\u2014however implies that sequencing of constitutional tissues could be clinically motivated. We conclude that\n                    <jats:italic>DICER1<\/jats:italic>\n                    mutations are amassed in younger patients with macrofollicular-patterned tumors and, most strikingly, atrophic changes. Given the rate of constitutional involvement, our findings could be of clinical value, allowing the pathologist to triage cases for genetic testing based on histological findings.\n                  <\/jats:p>","DOI":"10.1007\/s00428-024-03802-y","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T22:01:32Z","timestamp":1713477692000},"page":"105-114","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Atrophic changes in thyroid tumors are strong indicators of underlying DICER1 mutations: a bi-institutional genotype\u2013phenotype correlation study"],"prefix":"10.1007","volume":"485","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-5398","authenticated-orcid":false,"given":"Vincenzo","family":"Condello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3248-7629","authenticated-orcid":false,"given":"Adam","family":"Stenman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0031-0001","authenticated-orcid":false,"given":"Kartik","family":"Viswanathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5945-9081","authenticated-orcid":false,"given":"C. 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